Gallego M S, Ling B N
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Am J Physiol. 1996 Aug;271(2 Pt 2):F451-60. doi: 10.1152/ajprenal.1996.271.2.F451.
We used patch-clamp methods to investigate the effects of basolateral endothelin-1 (ET-1) on the amiloride-sensitive Na+ channel in A6 distal nephron cells. One hundred picomolar ET-1 decreased channel activity via an increase in mean time closed (P < 0.01, n = 10). Channel inhibition by pM ET-1 was mimicked by an ET-B receptor agonist (P < 0.05, n = 7) and was prevented by ET-B antagonists (P = 0.14, n = 10) but not by an ET-A antagonist (P < 0.05, n = 4). With the inhibitory ET-B receptor blocked, higher doses of ET-1 (10 nM) actually increased channel activity through an increase in mean time open (P < 0.001, n = 12). The current-voltage relationship and the number of channels were not changed by basolateral ET-1 exposure. We conclude that 1) basolateral ET-1 regulates amiloride-sensitive Na+ channels; 2) binding of picomolar ET-1 to ET-B receptors inhibits, whereas the binding of nanomolar ET-1 to a different ET receptor (likely ET-A) stimulates, channel activity; and 3) these dose-dependent, distal nephron responses provide a potential mechanism for the in vivo natriuresis and antinatriuresis observed in response to "subpressor" and "pressor" concentrations of ET-1, respectively.
我们采用膜片钳方法研究基底外侧内皮素-1（ET-1）对A6远端肾单位细胞中阿米洛利敏感的Na⁺通道的影响。100皮摩尔的ET-1通过增加平均关闭时间来降低通道活性（P < 0.01，n = 10）。ET-B受体激动剂可模拟皮摩尔浓度ET-1对通道的抑制作用（P < 0.05，n = 7），ET-B拮抗剂可阻止这种抑制作用（P = 0.14，n = 10），但ET-A拮抗剂不能（P < 0.05，n = 4）。在抑制性ET-B受体被阻断的情况下，更高剂量的ET-1（10 nM）实际上通过增加平均开放时间来增加通道活性（P < 0.001，n = 12）。基底外侧暴露ET-1后，电流-电压关系和通道数量未发生改变。我们得出以下结论：1）基底外侧ET-1调节阿米洛利敏感的Na⁺通道；2）皮摩尔浓度的ET-1与ET-B受体结合会抑制通道活性，而纳摩尔浓度的ET-1与另一种ET受体（可能是ET-A）结合则会刺激通道活性；3）这些剂量依赖性的远端肾单位反应分别为体内观察到的对“亚升压”和“升压”浓度ET-1的利钠和抗利钠作用提供了一种潜在机制。
